@article{e2f1e6d24a9e47f3bc3479449b22b139,
title = "Discovery of long-chain salicylketoxime derivatives as monoacylglycerol lipase (MAGL) inhibitors",
abstract = "Monoacylglycerol lipase (MAGL) is the enzyme hydrolyzing the endocannabinoid 2-arachidonoylglycerol (2-AG) to free arachidonic acid and glycerol. Therefore, MAGL is implicated in many physiological processes involving the regulation of the endocannabinoid system and eicosanoid network. MAGL inhibition represents a potential therapeutic target for many diseases, including cancer. Nowadays, most MAGL inhibitors inhibit this enzyme by an irreversible mechanism of action, potentially leading to unwanted side effects from chronic treatment. Herein, we report the discovery of long-chain salicylketoxime derivatives as potent and reversible MAGL inhibitors. The compounds herein described are characterized by a good target selectivity for MAGL and by antiproliferative activities against a series of cancer cell lines. Finally, modeling studies suggest a reasonable hypothetical binding mode for this class of compounds.",
keywords = "Cancer, Ketoxime, MAGL, Monoacylglycerol lipase inhibitors",
author = "Giulia Bononi and Carlotta Granchi and Margherita Lapillo and Massimiliano Giannotti and Daniela Nieri and Serena Fortunato and Boustani, {Maguie El} and Isabella Caligiuri and Giulio Poli and Carlson, {Kathryn E.} and Kim, {Sung Hoon} and Marco Macchia and Adriano Martinelli and Flavio Rizzolio and Andrea Chicca and Katzenellenbogen, {John A.} and Filippo Minutolo and Tiziano Tuccinardi",
note = "We are grateful to the University of Pisa (Progetti di Ricerca di Ateneo, prog. n. PRA-2017-51 and PRA-2018-18) and the National Institutes of Health (PHS 5R01015556 to J.A.K.) for funding. A. Chicca thanks Prof. Juerg Gertsch (Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland) for the valuable support to perform experiments and for inspiring discussions. We are grateful to the University of Pisa (Progetti di Ricerca di Ateneo, prog. n. PRA-2017-51 and PRA-2018-18 ) and the National Institutes of Health ( PHS 5R01015556 to J.A.K.) for funding. A. Chicca thanks Prof. Juerg Gertsch (Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland) for the valuable support to perform experiments and for inspiring discussions.",
year = "2018",
month = sep,
day = "5",
doi = "10.1016/j.ejmech.2018.08.038",
language = "English (US)",
volume = "157",
pages = "817--836",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson s.r.l.",
}